As a result of the disproportionately high incidence of coronary vascular disease (CVD) in the diabetic population, surgery is often required to clear or by-pass occluded coronary arteries or, at worst, replace the diseased heart. However, the mechanisms responsible for the initial progression of CVD in persons afflicted with insulin dependent diabetes mellitus (IDDM) or non-insulin dependent diabetes mellitus (NIDDM) remain intact. Thus, following coronary artery angioplasty, coronary by-pass graft surgery, or cardiac transplantation the diabetic patient may be predisposed to coronary restenosis or, in the case of the transplanted heart, the development of accelerated graft atherosclerosis (AGA). This study is designed test the hypotheses: 1) following coronary artery angioplasty or by-pass surgery, restenosis is accelerated and more pronounced in the diabetic, as compared to the non-diabetic patient; 2) the progression and magnitude of accelerated graft atherosclerosis (AGA) in the transplanted heart is greater in the diabetic patient than in the non-diabetic patient; and 3) coronary restenosis and the development of AGA following cardiac transplantation are associated with detective lipid metabolism in the diabetic patient. The proposed research will provide the Candidate with the opportunity to expand upon existing research interests and skills. I have characterized alterations in left ventricular function and capillary bed geometry following myocardial ischemia and reperfusion. I am very much interested in applying these techniques to the study of diabetes mellitus specifically, to evaluate alterations in the structure and function of the diabetic heart. To this end, I have collected preliminary morphometric data which lend support to the hypotheses is that reduced capillary surface area consequent to remodeling of the capillary bed may contribute to reduced capillary exchange capacity in these hearts. This, in turn, may result in decreased levels of energy-dependent cardiac function. It is my objective to continue to characterize alterations in myocardial structure and function in diabetics. Ultimately, it is my goal to contribute to a better understanding of diabetes and a treatment strategy for the diabetic patient, thus potentially improving not only the life expectancy, but the quality of life for persons afflicted with diabetes mellitus.